ZAVZPRET is indicated for the acute treatment of migraine with or without aura in adults.

ZAVZPRET is not indicated for the preventive treatment of migraine.

Nasal spray: 10 mg of zavegepant per device. Each unit-dose nasal spray device delivers a single spray containing 10 mg of zavegepant.

ZAVZPRET is contraindicated in patients with a history of hypersensitivity reaction to zavegepant or any of the components of ZAVZPRET

The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling:

ZAVZPRET (zavegepant) nasal spray contains zavegepant hydrochloride, a calcitonin gene-related peptide receptor antagonist. Zavegepant hydrochloride is described chemically as (R)-N-(3-(7-methyl-1H-indazol-5-yl)-1-(4-(1-methylpiperidin-4-yl) piperazin-1-yl)-1-oxopropan-2-yl)-4-(2-oxo-1,2-dihydroquinolin-3-yl) piperidine-1-carboxamide hydrochloride and its structural formula is:

Its molecular formula is C

Each unit-dose ZAVZPRET device for nasal administration delivers 10 mg of zavegepant (equivalent to 10.6 mg of zavegepant hydrochloride) in a buffered aqueous solution containing dextrose, hydrochloric acid, sodium hydroxide, and succinic acid in water for injection. The solution has a pH of 5.3 to 6.7.

The efficacy of ZAVZPRET for the acute treatment of migraine with or without aura in adults was demonstrated in two randomized, double-blind, placebo-controlled trials (Study 1 and Study 2). In both studies, patients were instructed to treat a migraine of moderate to severe headache pain intensity. Rescue medication (i.e., NSAIDs, acetaminophen, and/or an antiemetic) was allowed 2 hours after the initial treatment. Other forms of rescue medication such as triptans were not allowed within 48 hours of initial treatment. In Study 1 and Study 2, 13.4% and 13.6% of patients were taking preventive medications for migraine at baseline, respectively. None of the patients were on concomitant preventive medication that act on the CGRP pathway.

In Study 1 (NCT04571060), patients were randomized to receive a single dose of ZAVZPRET 10 mg (N=623) or placebo (N=646). Efficacy was demonstrated with ZAVZPRET 10 mg by an effect on the coprimary endpoints of pain freedom and most bothersome symptom (MBS) freedom at 2 hours after a single dose, compared to placebo. Pain freedom was defined as a reduction of moderate or severe headache pain to no headache pain, and MBS freedom was defined as the absence of the self-identified MBS (i.e., photophobia, phonophobia, or nausea). The most common MBS reported before dosing was photophobia (55%), followed by nausea (28%), and phonophobia (16%).

In Study 1, the percentage of patients achieving headache pain freedom and MBS freedom 2 hours after a single dose was statistically significantly greater in patients who received ZAVZPRET compared to those who received placebo (Table 2).

Figures 1 and 2 present the percentage of patients achieving migraine pain freedom and MBS freedom within 2 hours following treatment in Study 1.

In Study 1, statistically significant effects of ZAVZPRET compared to placebo were demonstrated for the additional efficacy endpoints of pain relief at 2 hours post-dose, return to normal function at 2 hours post-dose, sustained pain freedom from 2 to 48 hours post-dose (Table 3), and phonophobia and photophobia freedom at 2 hours post-dose. Pain relief was defined as a reduction in migraine pain from moderate or severe severity to mild or none. The measurement of the percentage of patients reporting normal function at two hours after dosing was derived from a single item questionnaire, asking patients to select one response on a 4-point scale: normal function, mild impairment, severe impairment, or required bedrest.

The incidence of photophobia and phonophobia was reduced following administration of ZAVZPRET 10 mg as compared to placebo.

In Study 2 (NCT03872453), patients were randomized to receive a single dose of ZAVZPRET 10 mg (n=391) or placebo (n=401).

In Study 2, statistically significant efficacy was demonstrated with ZAVZPRET 10 mg by an effect on the coprimary endpoints of pain freedom and most bothersome symptom (MBS) freedom at 2 hours after a single dose, compared to placebo. Pain freedom was observed in 22.5% of patients receiving ZAVZPRET and 15.5% of patients receiving placebo (p-value = 0.011). MBS freedom was observed in 41.9% of patients receiving ZAVZPRET and 33.7% of patients receiving placebo (p-value = 0.016). The most common MBS reported before dosing was photophobia (53%), followed by nausea (31%), and phonophobia (15%).

Advise patients to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Inform patients about the signs and symptoms of hypersensitivity reactions after administration of ZAVZPRET. Advise patients to contact their healthcare provider immediately if signs or symptoms of hypersensitivity reactions occur

Inform patients that hypertension can develop or pre-existing hypertension can worsen with ZAVZPRET, and that they should contact their healthcare provider if they experience elevation in their blood pressure

Inform patients that Raynaud’s phenomenon can develop or worsen with ZAVZPRET. Advise patients to discontinue ZAVZPRET and contact their healthcare provider if they experience signs or symptoms of Raynaud’s phenomenon

Advise patients to speak with their healthcare provider about any prescription or over-the-counter medications or herbal supplements that they take or plan to take. Inform patients that if they need to use an intranasal decongestant it should be administered at least 1 hour after ZAVZPRET administration

This product’s labeling may have been updated. For the most recent prescribing information, please visit

LAB-1544-2.0

ZAVZPRET is a prescription medicine used in adults for the acute treatment of migraine attacks with or without aura.

ZAVZPRET is not used to prevent migraine attacks.

It is not known if ZAVZPRET is safe and effective in children.

See the end of this leaflet for a complete list of ingredients in ZAVZPRET.

ZAVZPRET may cause serious side effects including:

The most common side effects of ZAVZPRET are:

These are not the only possible side effects of ZAVZPRET.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use ZAVZPRET for a condition for which it was not prescribed. Do not give ZAVZPRET to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about ZAVZPRET that is written for health professionals.

Active ingredients in ZAVZPRET: zavegepant

Inactive ingredients in ZAVZPRET: dextrose, hydrochloric acid, sodium hydroxide, and succinic acid in water for injection.

For more information, go to

LAB-1545-2.0

Zavzpret

PROFESSIONAL SAMPLE –NOT FOR SALE

Do not test spray,

U.S. Pharmaceuticals

LOT xxxxxxx

NDC 63539-135-01

PROFESSIONAL SAMPLE –

PEEL OFF

Zavzpret

Each unit-dose device contains 10 mg of zavegepant.

Pfizer

PROFESSIONAL

NDC 63539-135-02

Zavzpret

This box contains:

For Intranasal use only.

1 spray (10 mg dose) per unit.